Molecular Biology of the Cell by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morgan, Martin Raff, Keith Roberts, Peter Walter by by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morg

INTRODUCTION TO PATHOGENS AND THE HUMAN MICROBIOTA
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(A)
50 nm
effector protein
secreted into
host cell
host-cell
plasma
membrane
effector protein
produced bacteriumin bacterium
(B)
translocator
type III
secretion
apparatus
Figure 23–7 Type III secretion systems
that can deliver effector proteins into
the cytosol of a host cell. (A) Electron
micrograph of purified type III secretion
systems, each of which consists of
over two dozen proteins. (B) The large
lower ring is embedded in the bacterial
inner membrane, and the smaller upper
ring is embedded in the bacterial outer
membrane. During infection, docking of
the tip of the hollow needle at a host-cell
plasma membrane results in the secretion
of bacterial translocator proteins (green),
which form a pore in the host membrane,
through which bacterial effector proteins
are then secreted into the host cell.
(A, from O. Schraidt et al., PLoS Pathog.
6(4):e1000824, 2010.)
host cells (see Figure 23–6). The A subunits are called lethal factor and edema
factor. The A subunit of edema toxin is an adenylyl cyclase that catalyzes the production
of cyclic AMP (see Figure 15–25), leading to an ion imbalance that can
cause an accumulation of extracellular fluid (edema) in the skin or lung. The A
subunit of lethal toxin is a protease that cleaves several activated members of the
mitogen-activated protein kinase kinase (MAP kinase kinase) family (see Figure
15–49), disrupting intracellular signaling and leading to immune cell dysfunction
and cell death. Injection of lethal toxin into the bloodstream of an animal causes
shock (a large fall in blood pressure) and death.
Apart from toxins, bacteria use specialized secretion systems to secrete
MBoC6 m24.08/23.07
many other effector proteins that interact with host cells. Gram-negative bacteria
have a general secretion system and several classes of accessory secretion systems
(types I–VI). A subset of these accessory secretion systems, called contact-dependent
secretion systems, is present in many bacteria that contact or live inside host
cells. The type III secretion system (Figure 23–7), for example, injects into the
host-cell cytoplasm effector proteins that can elicit a variety of host cell responses
that enable the bacterium to invade or survive. There is a remarkable degree of
structural similarity between the type III syringe and the base of a bacterial flagellum.
Because flagella are found in a wider range of bacteria than are type III
secretion systems, and the secretion systems appear to be adaptations specific for
pathogenesis, it seems likely that the type III secretion systems evolved from flagella.
Other types of delivery systems used by bacterial pathogens appear to have
evolved independently. For example, type IV secretion systems are closely related
to the conjugation apparatus that many bacteria use to exchange genetic material.
Fungal and Protozoan Parasites Have Complex Life Cycles
Involving Multiple Forms
Pathogenic fungi and protozoan parasites are eukaryotes, as are their hosts. Consequently,
antifungal and antiparasitic drugs are often less effective and more
toxic to the host than are antibiotics that target bacteria. A second characteristic
of fungal and parasitic infections that makes them difficult to treat is the tendency
of the pathogens to switch among several different forms during their life cycles. A
drug that is effective at killing one form can be ineffective at killing another form;
therefore the population can survive the treatment.
Fungi include both unicellular yeasts (such as Saccharomyces cerevisiae and
Schizosaccharomyces pombe, which are used to bake bread and brew beer, and as
model organisms for cell biology research) and filamentous, multicellular molds
(like those found on moldy fruit or bread). Most of the important pathogenic
fungi exhibit dimorphism—the ability to grow in either yeast or mold form. The
yeast-to-mold or mold-to-yeast transition is frequently associated with infection.